The cytochalasins are a group of fungal metabolites which show extensive biological activity including (a) inhibition of cytokinesis, (b) inhibition of cell movement, (c) cell enucleation, (d) interference with blood platelet aggregation, (e) effects on blood clot breakdown, (f) effects on the release of growth hormones, (g) antiedemic activity, (h) abscess inhibition, and (g) antibiotic activity. Although these compounds are not yet used in human therapy, it is quite possible that cytochalasins, or related compounds, will eventually have practical application in medicine. Described as exemplary of the work to be done in this area are total syntheses of cytochalasin A and proxiphomin. We expect that this synthetic work will define the chemistry of these compounds in anticipation of future needs, and will make available unnatural derivatives should these compounds find a use in human therapy.